Various diseases which an active oxygen would be implicated in have been known from the past. Examples of such diseases are ischemic disorder (such as sequela of ischemic heart disease, sequela of cerebral infarction, or stress ulcers), reperfusion disorder, inflammatory disease (such as chronic rheumatism, nephritis, or asthma), cancer, diabetes, cataract, arteriosclerosis, drug toxinosis, pesticide toxinosis, hepatopathy caused by an excess administration of a drug or an excess taking up of a pesticide, retinopathy of prematurity, hyperesthesia optica, or disorder caused by radiation.
For the treatment of such diseases, administration of an enzyme exhibiting an active oxygen scavenging activity, for example, superoxide dismutase (hereinafter sometimes referred to as SOD) is considered effective. However, the half-life period of SOD in a living body is extremely short, and therefore, SOD should be administered in a large amount. When a long-term administration of SOD is required, it is necessary to take care of side effects, such as an anaphylactic shock caused by an antigen-antibody reaction, because the enzyme is a protein and has antigenecity. Further, there exist various problems, for example, in that no effect can be obtained from oral administration.
As one of non-protein compounds having the active oxygen scavenging activity, pterin derivatives are known. For example, Japanese Unexamined Patent Publication (Kokai) No. 6-56669 discloses that a pterin derivative or a neopterin derivative exhibits the active oxygen scavenging activity. Further, Japanese Unexamined Patent Publication (Kokai) No. 7-188232 discloses that the above-mentioned pterin derivative or neopterin derivative is effective against cytopathy caused by free radicals.
Neopterin (abbreviated to NP), i.e., 2-amino-4-oxo-6-(D-erythro-1',2',3'-trihydroxypropyl)-pteridine, is a typical compound of the above-mentioned pterin derivatives or neopterin derivatives and released from macrophages. Although the physiological functions of NP are not completely elucidated, it is known to have an antioxidative activity against active oxygens (for example, S. Kojima et al., FEBS, 304, 2, 3, 163-166, 1992; or S. Kojima et al., FEBS, 329, 1, 2, 125-128, 1993).
Further, it is known that 5,6,7,8-tetrahydroneopterin (abbreviated to NPH4), i.e., the reduced neopterin, has the potent antioxidative activity, and it is reported that NPH4 is effective against various diseases (for example, S. Kojima et al., FEBS, 304, 2, 3, 163-166, 1992; Icho et al., Biochemical Pharmacology, 45, 10, 1953-1958, 1993; or Arai et al., Neuroscience Letters, 173, 107-110, 1994).
Nevertheless, 5,6,7,8-tetrahydroneopterin (NPH4) exhibits teratogenicity, and therefore, a different non-protein compound having the active oxygen scavenging activity has been desired.
The inventors of the present invention engaged in intensive research to find non-protein compounds having the active oxygen scavenging activity, and as a result, found that a pterin derivative which has not been known to have the active oxygen scavenging activity actually exhibits such an activity. The present invention is based on the findings.